Transcript Case D – FBC Warm type Autoimmune Hemolytic Anemia

Case D – FBC
Warm type
Autoimmune Hemolytic
Anemia
Presented by:
Meme Phung
Zhi Yuan Quek
Alison Wong
Scenario
A 25 year old female presented with a 2 week history
of:
progressive tiredness and dyspnoea on exertion.
In the previous three weeks she had noted:
intermittent migratory arthralgia
Two years ago she had an episode of pleurisy.
She denied taking any medications.
Physical examination showed mucosal pallor with mild scleral
icterus. The spleen was palpable (3cm), and the joints
normal. Urinalysis showed a strong reaction to
urobilinogen, but was negative for bilirubin and blood.
Initial investigations included the
following:
Hb
65 g/L
115-165
MCV
99 fL
80-100
WCC
14.5X
109/L
Platelets
ESR
4.0-11.0
X109/L
350 X109/L 150-400
X109/L
58 mm/hr 3-9
Blood film
Moderate anisocytosis with numerous
spherocytes, prominent polychromasia and mild
red cell agglutination. Nucleated red cells were
present and there was a neutrophilia with
occasional band forms.
In view of the marked polychromasia, a
recticulocyte count was suggested.
*Recticulocyte 310 X 109/L
10-80 X 109/L (0.2(18%)
2.0%)
In this patient, warm type autoimmune haemolytic anaemia (AIHA)
is suspected.
Warm type autoimmune
haemolytic anaemia
(AIHA)
AIHA is an uncommon disorder due to a
malfunction of the immune system that produces
autoantibodies, which attack red blood cells as if
they were antigens.
Can occur at any age.
Affect women more than men.
Cause unknown (idiopathic autoimmune hemolytic
anaemia)
Destruction of RBCs (hemolysis) by
autoantibodies may occur abruptly or insidiously.
2 Main types of AIHA
1. Warm type antibody hemolytic
anaemia
2. Cold type antibody hemolytic anaemia
Warm type antibody
hemolytic anaemia
1. A warm reacting, positive direct antiglobulin
test, where IgG or C3 (complement C3) is
found on the RBC surface at 37C.
2. The antibody has its maximal activity at
37C,

 resultant hemolysis is called warm antibody
induced hemolytic anaemia.
3. Severe life threatening condition.
Clinical presentations
1. Symptoms:
Symptoms of anaemia (e.g. weakness, tired,
fever)
Slight splenomegaly (enlarged spleen)
Sudden onset of pallor
Exercise intolerance
Difficulty breathing
Jaundice
Dark urine
2. Clinical features:
Common features of hemolysis (LOW
hematocrit and Hb)
High MCHC
Autoagglutination
WCC elevated
Raised recticulocytes (=  immature RBCs)
Raised LDH
Low Haptoglobins (=protein in blood that
binds to free Hb)
Raised serum total bilirubin
Spherocytes and Red Cell
Agglutination
Agglutination = antibodies that agglutinate (‘clump
to’) RBCs, causing damage to the RBCs which is
subsequently removed in the spleen or liver in a form of
extravascular hemolysis.
The most common form of AIHA is incomplete or
non-agglutinating antibodies.
 antibodies bind to the RBC membrane, but in
insufficient quantity to cause intravascular hemolysis or
agglutination.
The RBC is then damaged, resulting in spherocyte
formation.
The RBC is not destroyed until they get phagocytocized
in the spleen or liver.
Agglutination
Figure 1. Autoagglutination is visible on the
sides of the blood tube.
Figure 2. Microscopic agglutination of
erythrocytes is visible in this blood smear
Spherocytes
Figure 3. Typical spherocyte, appearing as a small erythrocyte that lacks
central pallor because of its spherical (rather than biconcave) shape
Significance of presence of
spherocytes:
Show evidence of active hemolysis
they’re spheroid because of lost
membrane mass.
Spherocytes are common features of
warm antibody hemolytic anemia
Elevated MCHC may be a clue to the
presence of spherocytes
From the patient’s blood film
results:
Blood film:
moderate anisocytosis with numerous
spherocytes
prominent polychromasia and mild
red cell agglutination.
Nucleated red cells were present and there
was a neutrophilia with occasional band
forms.
Warm type AIHA is
suspected…
Need to confirm diagnosis with Coomb’s
antiglobulin test.
Direct Antiglobulin Test
(DAT) / Coomb’s Test
What is it?
To detect the presence of autoantibodies
against the body’s own red blood cells
Antibodies sometimes destroy red blood cells
and cause anaemia
Hallmark of AIHA  warm-reacting, postive
DAT

IgG or C3 found on RBC surface at 37oC
Principle Behind
Results
positive or negative
 false negative test results

 perform dilutions of the Coombs’
reagent to decrease the chance of false
negative reactions

false positive test results rarely occur
3 Types of Direct
Antiglobulin Reactions
1. Direct antiglobulin positive with antiIgG and negative with anti-C3

idiopathic AIHA and in -methyldopaand penicillin-induced cases
2. Direct antiglobulin positive with antiIgG and anti-C3

SLE and idiopathic AIHA, not in drugassociated cases
3. Direct antiglobulin positive with anti-C3
but negative with anti-IgG
idiopathic AIHA when IgG antibody low affinity,
in some drug-associated cases and in cryopathic
forms

Back to patient:


DAT positive; both IgG and complement
demonstrated on red cells
Signs and symptoms of SLE and not
taking medications
Conditions & Medications
Associated with warm
AIHA
Disease associations with AIHA:
1.
2.
3.
4.
5.
6.
Idiopathic
Infections
Neoplasms/Malignancies
Autoimmunity
Immune deficiency
Miscellaneous
Drug associations with AIHA:
(eg. -methyldopa, levodopa, high-dose penicillin
or cephalosporins, gold)

Mechanisms implicated (when
DAT positive)
a) Drug absorption mechanism
(hapten mechanism)
b) Immune complex mechanism
(“innocent bystander”
mechanism)
c) Autoantibody mechanism
d) Membrane modification
mechanism
Patient has history of arthralgias and
pleurisy, suggesting SLE
 underlying disease associated with
her AIHA
Systemic Lupus
Erythematous
What is SLE?
Is an autoimmune disorder
The cause is usually unknown
Occurs predominantly in younger women
Is a chronic inflammatory connective tissue
disorder that can involve joints, kidneys,
mucous membranes and blood vessel walls.
It can range in severity from mild to life
threatening.
What are the symptoms?
Fatigue, fever, anorexia, nausea weight loss, joint
pain, and arthritis
muscle pain facial or other skin rash, often made
worse by sun exposure (commonly a "butterfly
rash" that occurs over the nose and cheeks of
the face)
hair loss, depression, confusion, headache, chest
pain, dry eyes and/or dry mouth
repeated miscarriages
Characteristics of Lupus
At least four of the following symptoms are generally present
for a diagnosis to be made:
 Malar rash
 Discoid rash
 Photosensitivity
 Oral ulcers
 Arthritis
 Serositis
 Leucopoenia (< 4000 mL), lymphonia (< 1500 /mL),
haemolytic anaemia or thrombocytopenia (< 100,000/
mL)
 Neurologic disorder
 Anti-DNA antibody, anti-Sm antibody or evidence of
antiphospholipid antibody
 Antinuclear antibodies on raised titer
Laboratory Findings
The fluorescent test for ANA (antinuclear antibody) screens for SLE
It is present in a very high percentage
(over 90%) of lupus patients
Positive ANA tests (usually in high titer)
occur in > 98 % of SLE patients
Laboratory Findings
Leads to more specific tests for anti-double
stranded DNA antibodies
High titers of anti-double stranded DNA
antibodies are highly specific for SLE
Other ANA and anticytoplasmic antibodies are
diagnostically valuable in SLE
eg anti-Ro, anti Sm, anti La, RNP, Jo-1
False positive serologic tests for syphilis occur
in 5 to 10% of SLE patients
Table 1. Numbers (percentage) of patients
with SLE with anti-dsDNA antibodies and
antinucleosome antibodies (n=95)
From: Cairns: Ann Rheum Dis, Volume 62(3).March
2003.272-273
Treatment
Mild Lupus

NSAIDs, low dose Aspirin,
hydroxychloroquine,chloroquine
Severe Lupus

immediate corticosteroid such as
prednisone sometimes immunosuppressive
drugs azathioprine or cyclophosphamide
Conclusion
Patient diagnosed with warm type AIHA
This patient has a history of arthralgia
and pleurisy suggesting SLE.
Patient needs to confirm the diagnosis
of SLE with a ANA test and anti-double
stranded DNA test
Haemolytic anaemia is associated with
severe SLE which may require
immediate corticosteroid therapy